Protocatechuate 3,4-dioxygenase mechanism

Since much information has been obtained for protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa in the past decade, the mechanism proposed for in-tradiol cleavage is based on the studies of this enzyme. 

Heavy metal cations (e.g., Pb2+, Hg2+) and oxyanions (e.g., UOf ) are toxic to bacteria although resistance may be induced by various mechanisms after exposure. Attention has been drawn to an unusual example in which Al3+ may be significant since the catechol 1,2-dioxygenase and protocatechuate 3,4-dioxygenase that are involved in the metabolism of benzoate by strains of Rhizobium trifolii are highly sensitive to inhibition by Al3+ (Chen et al. 1985). 

The intradiol cleaving catechol dioxygenases are bacterial iron-containing enzymes that serve as a component of nature s mechanism for degrading aromatic compounds in the environment. These enzymes, represented by catechol 1,2-dioxygenase (CTD) and protocatechuate(3,4-dihydroxybenzoate) 3,4-dioxygenase (PCD), catalyze the reaction... 

The active site within protocatechuate 3,4-dioxygenase (the enzyme that effects reaction 8, with R = CO2H), as determined crystallographically, is high spin, 5-coordinate Fe(ni) containing 2 tyrosine and 2 histidine ligands, and a coordinated water or hydroxide ((1), see Fig. 1), and a postulated mechanism, based largely on EXAFS and EPR data, for the... 

Figure I. Possible mechanism for the action of protocatechuate 3,4-dioxygenase O implies 0, R = C02 adapted front ref. 3.

In the mechanism of the intradiol oxygenation, the first step is the activation of catechol by coordination to a Fe(III) center. The chelate coordination of catechols in the enzymatic systems (protocatechuate 3,4-dioxygenase, 3,4-PCD) has been clarified by the X-ray analysis. in addition, the analysis indicated... 

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